DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-19 are under examination.
Response to Applicants Amendments/Arguments
Applicants made significant amendments to the clams. Because of the recent claim amendments, the claim objections have been removed. The amendments clearly specify that the disorders that are treated include fibromyalgia or chronic fatigue syndrome. Therefore, the written description rejection is removed. The amendments have corrected the indefiniteness in the clams and the 112(b) rejection is withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Enablement Rejection
Claims 1-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQQ2d 1400 (Fed. Cir. 1988). While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experiment to make and use the invention based on the content of the disclosure is undue.
Nature of the Invention:
The claims recite a method of treating fibromyalgia or chronic fatigue syndrome wherein the whole underlying pathophysiology of the disease is directly linked to altered gut bacteria/dysbiosis. The method involves intravenously administering platelet-rich plasma concentrate directly into the blood stream of the patient to cause systemic release of platelet growth factors and peptides in the patient to improve gut biome of the patient and promote systemic circulatory repair by blood vessel formation.
Breadth of the Claims
The claims encompass treating a patient with fibromyalgia or chronic fatigue syndrome whose underlying pathophysiology is directly linked to altered gut bacteria/dysbiosis. The claims state that conditions such as fibromyalgia or chronic fatigue syndrome can be treated by intravenously administering about 7 ml of an autologous platelet-rich plasma composition having a concentration of at least 2x106 platelets/µL directly into a bloodstream of the patient. The breadth of the claims are so broad that an amount of at least 2x106 or more platelets/µL can be successfully used to treat unwanted conditions such as fibromyalgia or chronic fatigue syndrome directly linked to altered gut bacteria/dysbiosis. Administering the platelet rich plasma intravenously can improve the gut biome and promote circulatory repair by promoting blood vessel formation.
Teachings of from the Prior Art:
Minerbi et al. (2020, Clin Exp Rheumatol) suggest that the gut bacteria are involved in the pathogenesis of numerous medical conditions in a variety of medical fields including gastroenterology, metabolic, rheumatologic, neurologic and psychiatric disorders, and evidence is mounting that gut bacteria could also play a role in chronic pain and specifically fibromyalgia (Abstract). While this teaching suggests the involvement of gut bacteria, gut dysbiosis, or altered gut bacteria with numerous conditions; however, there is no evidence presented that gut dysbiosis is directly linked to pathophysiology of fibromyalgia or chronic fatigue syndrome.
Applicants Specification/Guidance Working/Examples:
The specification discloses that evidence has demonstrated and established both angiogenic and bactericidal doses of PRP (para. [0006] in Page 2). These doses chosen to encompass both established angiogenic and bactericidal in-vitro dose capabilities. At most, the effect of bactericidal activity of PRP is based on in vitro experimentation, and there is no indication that in vivo administration of PRP intravenously would result in killing specific bacteria and achieving therapeutic benefit for patients having fibromyalgia or chronic fatigue syndrome. Prior art recognizes the bactericidal activity of PRP in in vitro experimentations (see Drago et al. 2013, BMC Microbiology). Sethi et al. (2021, J. Cardiothorac. Surg.). These references suggest a potential of PRP as antibacterial agent in managing wounds. However, none of prior art available suggests IV-PRP produces bactericidal effect. It is understood that PRP at the claimed dose would not be maintained upon intravenous injection, and it is not conceivable that the claimed effects which were observed in vitro when the concentration is maintained would be present in vivo without any evidence. There is no connection in the bactericidal effect of PRP in vitro and the alleged functionality in achieving therapeutic benefit in patients having fibromyalgia or chronic fatigue syndrome.
Regarding blood vessel formation, there is no known prior art teaching any correlating neo-vascularization with achieving therapeutic benefit to patients. The instant specification merely states that angiogenesis (new blood vessel formation) is often necessary for tissue genesis (para. [0006]). However, the specification does not elaborate how fibromyalgia or chronic fatigue syndrome requires tissue genesis or angiogenesis in order to achieve therapeutic benefits.
The instant specification also discloses “[w]hile it has been shown that a minimum of 1.5×106 platelets/μL stimulates new blood vessel formation and inhibition was shown at 3.0×106 platelets/μL, this has only been demonstrated one time in the clinical literature for hair restoration.” (para. [0008 of the specification]). There is no clear description or evidence supporting that angiogenesis or neo-vascularization as required in the claimed method for achieving one or more therapeutic benefits for fibromyalgia.
It is known in the art that PRP could be able to induce neo-vascularization in vitro and in vivo (see Kakudo et al. 2014, Med. Mol. Morphol.) as well as the instant specification. However, it is not known in the art that angiogenesis or neo-vascularization in the patients with fibromyalgia or chronic fatigue syndrome would produce any therapeutic benefits. While Kakudo et al. teach in vivo as well as in vitro data showing that PRP promotes angiogenesis, however, the in vivo data were based on PRP gelled in vitro and implanted subcutaneously in the mice (p.85, In vivo angiogenesis assay). There is no prior art available teaching neo-vascularization caused by PRP when injected intravenously. The instant specification does not provide any evidence supporting the neo-vascularization effect of PRP when injected intravenously. While it is known in the art that PRP promotes neovascularization when administered into local lesions, there is no prior art teaching IV-PRP would promote neovascularization. In the lack of evidence present in prior art as well as the instant specification, it is highly unpredictable to a person skilled in the art to cause neovascularization by injecting PRP intravenously with the dosage as claimed in the patients with fibromyalgia or chronic fatigue syndrome and thus achieving one or more therapeutic benefits.
Furthermore, the claims state that any amount of at least 2x106 platelets/µL can be used to treat fibromyalgia or chronic fatigue syndrome. However, the specification does not provide convincing evidence showing what the desired treatment concentration is when treating either fibromyalgia or chronic fatigue syndrome specifically. The claim doesn’t have an upper limit and can include platelet counts of 400,000 platelets/µL or more which is capable of causing a dangerous platelet condition called thrombocytosis.
As acknowledged by applicant, IV-PRP is different from intra-articular PRP, which is well known in the art for treating pain, and thus, there is no expectation of success for IV-PRP causing neo-vascularization without any evidence or working embodiment showing neo-vascularization caused by IV-PRP, particularly when the prior art does not recognize such effect by IV-PRP. The instant specification does not provide any guidance or enabling embodiment showing that IV-PRP as claimed would necessarily produce neo-vascularization and the neo-vascularization leads to one or more therapeutic benefits to the patients with fibromyalgia or chronic fatigue syndrome. There is no guidance or working embodiment showing any evidence that IV-PRP would result in any therapeutic benefits to fibromyalgia or chronic fatigue syndrome.
The pharmaceutical art is highly unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to the therapeutic effects, whether or not the IV-PRP would be effective for inducing neo-vascularization as claimed and thus producing effective therapeutic outcome for fibromyalgia or chronic fatigue syndrome.
M.P.E.P. § 2164.03 reads, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The ‘amount of guidance or direction’ refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004) (“In applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required.”).
Considering lack of any evidence showing any therapeutic benefits in treating fibromyalgia by IV-PRP, lack of guidance or working example showing effective treatment of fibromyalgia or relieving symptoms thereof, and highly unpredictable nature of the claimed method, it is concluded that undue experimentations are required to make/use the claimed invention.
Response to Applicants Arguments/Amendments
Applicants argue that the claimed invention is indeed enabled by pointing to examples in the specification. Applicants point to paragraph 41 of the specification specifically.
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This is a hopeful paragraph about designing a successful PRP therapy in the future. This paragraph provides no solid data on how to treat undesirable conditions such as fibromyalgia or chronic fatigue syndrome using an intravenous dose of PRP.
Applicants further argue that gut bacteria profile can play a role in chronic disease syndrome. However, the specification does not clearly establish a specific amount of PRP that is able to effectively impact the gut bacteria profile in a manner that improves the symptoms of a target disease such as fibromyalgia or chronic disease syndrome. An effective dose for each condition has not been established. There is no evidence presented that show an effective dose capable of impacting the gut biome in a manner that ameliorates the symptoms of either fibromyalgia or chronic disease syndrome. The claims just recite a amount with no capped upper limit.
Applicants argue that the amount of PRP administered is at least 33% greater than the amount associated with effective localized administration. However, the specification does not provided evidence of intravenously administered doses to a subject which successfully impact the biome of an individual in a manner that improves the fibromyalgia or chronic disease syndrome. There is no evidence that shows how PRP treats fibromyalgia or chronic disease syndrome by causing blood vessel formation/systemic circulatory repair.
Conclusion
All claims stand rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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